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Drugs that clog ‘waste disposal’ may treat aggressive breast cancers

In a new paper in , a team led by , PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine reports “triple-negative” may be vulnerable to drugs that attack the proteasome. This cellular structure acts as the cell’s waste disposal, breaking down damaged or unneeded proteins.

These cancers, which lack the three major therapeutic markers for – the estrogen, progesterone and HER2 receptors – are very aggressive and difficult to treat. They mostly affect younger women and have the worst prognosis of all breast cancers.

By selectively turning genes off throughout the genomes of triple-negative tumor cells in vitro, Lieberman’s team found that these cells absolutely require active proteasomes in order to live. When turned off, the cells die.

These data suggest that triple-negative breast cancers may respond to treatment with drugs similar to bortezomib (Velcade®), a proteasome inhibitor that revolutionized the care of patients with the blood cancer multiple myeloma.


The study was supported by the Department of Defense Program, the National Cancer Institute (grant number R01CA146445) and the Foundation.

A Genome-wide siRNA Screen Identifies Proteasome Addiction as a Vulnerability of Basal-like Triple-Negative Breast Cancer Cells

Cancer Cell, Volume 24, Issue 2, 182-196, 12 August 2013. 10.1016/j.ccr.2013.07.008

Boston Children’s Hospital